In the News: Initial access type in dialysis patients and inflammation?

Fistula, graft or catheter placement, which causes more inflammatory response?? No one knows.

The authors conducted a prospective observational study in an incident HD population. C-reactive protein (CRP), interleukin-6 (IL-6), and interferon-γ-induced protein (IP-10) were measured before and at 6-time points after access placement for 1 year. 40 patients were studied with no differences in baseline characteristics. The study found that patients who initiate hemodialysis with a perm cath or an AVG have a heightened state of inflammation, which may contribute to the excess 90-day mortality after HD initiation.

This study is unique in that baseline cytokine values were obtained before first access placement and prior to HD initiation, so some comparison could have been done.  The prospective study design allowed for recording all intercurrent events, which were included in the adjusted analysis. 


Interestingly, this is showing us that any "foreign" object in our body is going to raise the inflammatory markers. AVF doesn't really involve an foreign body and perhaps these results reflect that more than the procedure. The numbers are small and larger studies are needed to clearly clarify this point


The full study is at
http://www.hindawi.com/journals/ijn/2012/917465/

In the News: ESA dose responsiveness? Some thoughts

A Japanese study just recently published in AJKD looked at dose responsiveness to ESA and effect on mortality. They defined 6 categories of ESA responsiveness based on a combination of ESA dosage.  They studied the relationship between hemoglobin level, ESA responsiveness and outcomes among hemodialysis patients. The authors found that mortality in patients on hemodialysis may be affected by ESA responsiveness and by the interaction of hemoglobin and ESA dose. Low hemoglobin level and high ESA dose were strongly associated with an increased risk of mortality. 

Dr Steven Fishbane and Azzour Hazzan wrote an editorial to the article in nature nephrology. 

Dr Hazzan puts his thoughts as a post here as well:

Recently there have an intense interest in anemia in patients with CKD and how best to manage it. In the early years of dialysis, anemia was found to be more common in patients with CKD and associated with higher mortality. This has been proven through many studies albeit not of a good quality-RCTs. However; recently we have found that our approach to normalize the hemoglobin level may have been  counterproductive. The reason being; increase stroke risks and probably higher cardiovascular mortality as well. Of the more definitive studies- the TREAT- looked at about 4000 patients with diabetic  CKD-Non dialysis. The treatment arm was darbepoetin to achieve levels of 13 versus using darbepoetin to keep HGb from falling under 9. The investigators found that patients with hemoglobin artificially driven towards normal,  had double fatal and non-fatal strokes risks. The question is why?

There are many stipulations. One possibility is the ESA dose effect? and patient's response to ESA. 

The above mentioned study by Fukuma et al. has investigated the relationship between hemoglobin level, erythropoietin responsiveness and outcomes among Japanese hemodialysis patients. The authors found that mortality in patients on hemodialysis may be affected by ESA responsiveness and by the interaction of hemoglobin and ESA dose. Our editorial piece looks into that and other studies. Basically it would be hard with this kind of studies to make any definitive conclusions to answer this question. Is it the EAS dose or is it  the fact that more severe anemia signify sicker patients and therefore higher mortality? In other words; acute and chronic illness, severity of illness, inflammation and co-morbidity are all highly intertwined with hemoglobin level and ESA dose, making analysis vulnerable to severe confounding variables.

In summary, we should exercise caution in treating anemia and use the lowest dose possible. 

Post by Dr. Azzour Hazzan

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/21890255

http://www.ncbi.nlm.nih.gov/pubmed/22009249

Topic Discussion: H1N1 vaccine in Transplantation

An interesting paper by. Katerinis et al. recently investigated the role of vaccination with the adjuvanted H1N1 vaccine in causing the production of anti – HLA antibodies in kidney transplant recipients.

This study was carried out in four cohorts of patients in Switzerland, 92 transplant recipients who had HLA antibodies checked before and 6 weeks after H1N1 vaccine, 59 transplant recipients who had been tested for HLA antibody up to 6 weeks before vaccination then again 4-8 weeks after, patients on the wait list for renal transplantation and a historical cohort from 2008 who never received the H1N1 vaccine.  In the first two cohorts 17.3% and 11.9% of patients developed anti-HLA antibodies (some donor specific while some were not) verses no patients in cohort III and 6.1% of patients in the historical cohort.  Six months after immunization the antibodies disappeared in the majority of patients.  There were two events that could have been attributed to the antibodies: one patient who developed a C4d negative thrombotic angiopathy in the kidney and another patient who developed antibody mediated rejection (however, authors report that he was non-compliant with his immunosuppression).

This is the first study in which antibody responses after H1N1 influenza vaccination led to a significant degree of HLA-antibodies.  The authors point out possible explanations including shared epitopes between influenza hemagglutinin and neuraminidase in the vaccine and HLA proteins, HLA antigens triggering a B-cell response toward the vaccine antigens, nonspecific reactions between vaccine antibodies and the antibody detection assay, and the adjuvanted vaccine triggering allosensitization by stimulating the innate immune system.

Even though there were novo HLA antibodies it is important to note that the authors do not recommend avoiding the vaccination as influenza in the transplant patients can be life threatening and the presence of these de novo antibodies were of low titer and probably not related to clinical events.  However this paper supports further studying the ability of adjuvanted vaccines in causing HLA-antibodies and possibly organ dysfunction.

Ref: I. Katerinis et al: De Novo Anti-HLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. Am J Transplant 2011;11:1727-1733

Post by Dr.Vinay Nair

ASN Abstracts 2011 online

ASN 2011 abstracts are now online live at
http://www.asn-online.org/education_and_meetings/kidneyweek/archives/KW11Abstracts.pdf

Check out the google page of ASN as well

http://www.google.com/reader/shared/06308306117959986613?c=CM_W4__Z9KsC

Topic Discussion: Re transplantation after BK Nephropathy

A recent paper in Transplantation ( multi institutional) looked at this exact question. How safe and well do patients when they get a re transplantation of the kidney after failed prior transplant from BK Nephropathy.
This retrospective study evaluated 31 patients from 6 centers.  26/31 had documented clearance of viremia and 13 underwent transplant nephrectomy before the new transplant.  Only 2 patients in the new transplants got BK nephropathy.  7/31 had acute rejection.  The patients who had BK viremia and replications had higher 1 year creatinine.  One graft was lost due to rejection. But overall, majority did well. Based on this small trial, the authors conclude that re transplantation is safe and effective for patients with prior graft loss due to BK Nephropathy but preferably post BK viral clearance.


Take a look at the full article at:
http://www.ncbi.nlm.nih.gov/pubmed/21836535

CLINICAL CASE 45: Answers and Summary

A 15 Y OLD MALE PRESENTS WITH 23GM OF PROTEINURIA. A COURSE OF STEROIDS LEADS TO NO IMPROVEMENT. RENAL FUNCTION IS NOW DECLINING. A KIDNEY BIOPSY IS PERFORMED. SMPDL-3B EXPRESSION on THE PODOCYTE HAS BEEN STUDIED IN ONLY THIS GLOMERULAR DISEASE.

Minimal Change     9%

FSGS                    70%

Membranous GN   3%

IgA Nephropathy  1%

Immunotactoid GN   9%

IgM Nephropathy   5%


The correct answer is FSGS. It has been suggested that rituximab might treat recurrent FSGS through an unknown mechanism. Rituximab not only recognizes CD20 on B lymphocytes, but might also bind sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b) protein and regulate acid sphingomyelinase (ASMase) activity. A recent study of 41 patients  at high risk for recurrent FSGS, 27 of whom were treated with rituximab at time of kidney transplant. SMPDL-3b protein, ASMase activity, and cytoskeleton remodeling were studied in cultured normal human podocytes that had been exposed to patient sera with or without rituximab. 


Look at a prior post regarding this
http://www.nephronpower.com/2011/08/in-news-rituximab-targeting-podocytes.html

ANIO event at ASN 2011

American Nephrologists of Indian Origin (ANIO) is having its annual dinner at ASN Nov 2011 this year.
The overall purpose of ANIO is to bring together like-minded nephrologists, nephrology trainees and health care professionals in the field of nephrology who have their origins in the Indian subcontinent and/or those who have worked in areas related to the Indian subcontinent. While the group is principally drawn from the United States, ANIO seeks to have a broader reach and would aim to draw membership from other parts of the world.


The event details can be found at www.an-io.com

The American Nephrologists of Indian Origin (ANIO) invite you to join
us for a reception and dinner at the American Society of Nephrology
Meeting 2011

We will be recognizing two outstanding colleagues for their
contributions to nephrology:

Dr. Karl Nath, Mayo Clinic
Dr. Ravi Thadhani, Massachusetts General Hospital

6:45 pm
Thursday, November 10, 2011
Marriott Hotel
1201 Market Street
Philadelphia Downtown
Philadelphia, PA 19107
(215) 625-2900Venue: Marriott Downtown, Philadelphia, PA

Special talk:
Understanding Hyponatremia: Treating Beyond the Primary Diagnosis

Ekambaram Ilamathi, MD
Medical Director,
Suffolk Nephrology Consultants, NY

CONSULT ROUNDS: Expressive Aphasia in ESRD

Expressive aphasia in a hemodialysis patient? What does one think of as a differential diagnosis?

1. Rule out Stroke/TIA.
2. Seizures
3. Dialysis associated dementia
4. Aluminium toxicity
5. Micro bubbles associated injury

CNS injury in dialysis can be from multiple causes: uremia, anemia, electrolytes, acid base, drugs, trace elements, aluminium, dialysis disequilibrium, impaired cerebral circulation and hypertension.

Lets discuss the last 3 a little bit more in detail. What is Dialysis associated dementia? This was a syndrome that was first described in 1972 which was also called dialysis encephalopathy and can occur as early as 15 months on dialysis to as long as seven years.  Interestingly, the first sign of presentation is a speech disorder:- stuttering or slurring of speech- can even be mutism.  Agitation and hallucinations are not uncommon. Usually, the stroke workup, lumbar puncture and metabolic workup is negative.  Usually, the symptoms are intermittent with worse at the end of dialysis. EEG maybe abnormal showing some high voltage theta and delta waves after dialysis.
This is different from dialysis disequilibrium syndrome. Dialysis dialysis or transplantatation doesn't change the course of the dementia.  Later literature on this suggests that this might be a variant of vascular dementia or a combination of alzheimer and vascular dementia.
Some studies might link dementia as above to aluminium toxicity and perhaps that might be the case as the symptoms of aluminium toxicity are also similar.
Microbubbles have been detected in dialysis patients.  These originate in extracorpeal lines and tubing of hemodialysis machine and circulate in the blood stream until they lodge perhaps in a organ. Air emboli can lead to some CNS changes and eventually dementia in HD population.  2-5% of physiologic right to left shunt can allow the mircobubbles to get to the brain and if someone has a PFO, even more.

Besides acute events, there are other factors in ESRD patients that can lead to expressive aphasia.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21590619
http://www.ncbi.nlm.nih.gov/pubmed/19724248
http://www.ncbi.nlm.nih.gov/pubmed/18363602

Topic Discussion: TIM molecules and Kidney Transplantation

TIM is "T cell immunoglobulin mucin". They are molecules that have shown to play a major role in immune responses. TIM 1,3 and 4 are the ones mainly noted in the literature.  TIM-1 and 3 are more on T cells and Tim-4 on Antigen presenting cells.

TIM 1:- Expression is on CD4+T cells, B cells, Mast cells and NK cells.  The proposed ligands for this molecule are TIM-4, IM3, and IgA and heavy chain to name a few.  The role in innate immunity is mediating clearance of apoptotic bodies and maintenance of peripheral tolerance.  In adaptive immunity, it increased th2 differentiation. Disease models include increased expression Asthma, MS, Sarcoidosis, and epithelial cells in AKI( also called KIM-1)

TIM3:- Expression on TH1 and Th17 cells, CD8+T cells and Antigen presenting cells.  Innate immunity wise limits macrophage expansion and modulates CD80 and CTLA-4 expression on antigen presenting cells.  It also helps in peripheral tolerance.  Disease models include T cells in chronic malignancy and infection.  Down regulated in Asthma and MS

TIM4:- Expression on dendritic cells and macrophages.  Ligands are TIM 1 and CD4+ t cells.  It up regulates Th2 responses and proliferation of activated T cells.  Disease model is food allergies and Asthma.

The TIM family is appearing as modulators of the immune system and helps in co stimulation of T cells. More will come about these molecules to improve our understanding of transplant immunology.


ref:
http://www.ncbi.nlm.nih.gov/pubmed/17331850
http://www.ncbi.nlm.nih.gov/pubmed/21906254
http://www.ncbi.nlm.nih.gov/pubmed/20536563
http://www.ncbi.nlm.nih.gov/pubmed/16938542

HHV-8 in Transplantation

Ariza-Heredia et al. published an interesting review of HHV8 associated complications in Transplantation this month.  The review, of which the major points are highlighted below, cover the pathogenesis, epidemiology, clinical presentation, diagnosis and treatment, and prevention of HHV-8. 

Pathogenesis of HHV-8

After primary infection HHV-8 establishes latency in CD19 B cells.  It can exist in a latent phase and beinduced to transition to the lytic state.  The trigger of this transition is unknown, however, once in the lytic phase several genes are upregulated increasing the progression of the cell cycle, Bcl-2 protien preventing apoptosis, secretion of IL6 (promotes B-cell proliferation) and angiogenic cytokines which stimulate VEGF. 

Epidemiology and Risk Factors.

Seroprevalence ranges from 4-7% in the U.S. to 5-20% in the Mediterranean and > 50% in zones of Africa and Amazon basin.  The solid organ transplant population in the U.S.  has been shown to have a higher rate of seropositivity (15%).  The chance of developing an HHV-8 related complication is highest among patients from countries with a high seroprevalence rate.  Infection can occur from reactivation of latent infection or primary infection.  Transmitting via organ transplant has also been reported. 

Clinical presentation

Primary infection in immunocompromised patients is often characterized by fever, splenomegaly, rash, lymphoid hyperplasia and pancytopenia – similar to many other viral infections.  Other classically associated diseases include Kaposi’s Sarcoma, Primary Effusion Lymphoma  (PEL)and Castleman’s disease.  In solid organ recipients the incidence is greater in patients who are males, older age, travel or reside in Africa or the Middle East, are mismatched at the HLA-B locus and who have been treated with  antilymphocyte globulin.  In the US the incidence has been reported as 8.8 cases/ 100,000 person years.  KS most commonly affects the skin (90% of cases) whereas visceral involvement occurs in only about 25% of kidney transplant recipients.  PEL is a rare form of non-Hodgkin’s lymphoma which can either present as lymphomatous involvement of serosal serfaces (classic PEL) or tissue-based tumors with a poor prognosis (solid PEL).  Cells can be HHV-8 postitive or HHV-8/EBV double-positive.  Only few case reports have been documented in solid organ recipients.  Castleman’s disease is characterized by IL-6 overexpression which results in lymph node hyperplasia either unicentric, or multicentric.  Patients usually present with lymphadenopathy, effusions, higher fevers and may even has concomitant KS lesions.  Again, this complication is very rare in solid organ transplant recipients. 

Diagnosis

Serology has limited utility.  Antibodies can be detected against the latent phase antigen LANA-1 or the lytic antigen (ORF65 and K8.1) which correlate better with high HHV-8 viral loads.  HHV-8 DNA quantification in plasma and PBMC’s can also be performed.  In addition, immunohistochemical staining can be performed on human tissue confirming active infection. 

Treatment

The major treatment of HHV-8 is reduction of total immunosuppression.  Sirolimus also has been used for the treatment of KS and other HHV-8 disease.  If there is no improvement with the above strategies chemotherapy such as CHOP has also been employed.  Castleman’s disease can be cured with surgical excision if unicentric, while treating multicentric disease may entail therapy with rituximab, anti-IL6 receptor antibodies  and antiviral medications.  Of the antiviral agents, ganciclovir, foscarnet and cidofovir have in vitro activity against HHV-8 making them a potential treatment or prevention modality.  Unfortunately good in vivo and prospective data on treatment and prevention does not exist. 

In summary, HHV-8 is an important etiologic agent for transplant associated complications/ malignancies especially for those from endemic regions.  A variety of diagnostic and therapeutic treatments exist though recognition of the clinical syndrome and reduction of immunosuppression remain the cornerstones of treatment. 

Ref. Ariza-Heredia et al: Human Herpes Virus 8 in solid Organ Transplantation. Transplantation 2011;92:837-844

Post by Dr. Vinay Nair

Patient Perspective: Give us the Choice by Kamal Shah

Give us the choice

Most people in India, when diagnosed with kidney failure are advised to get their fistula surgery done. Which is great in one way because the fistula, as we all know, is the gold standard when it comes to vascular access for hemodialysis.

However, I have often wondered why the PD catheter is not offered to the patient as an alternative to the fistula? Or a registration on the cadaver transplant list? Why is it almost always the fistula?

When I was diagnosed with kidney disease at the age of 22 in July 1997, I was given an AV shunt because my kidneys were expected to revive in a matter of weeks. Of course that never happened and I graduated to a fistula eventually - probably the first sign that my kidneys are not going to ‘jump back to life’! I got to know of PD only after my failed transplant, a good eighteen months after my initial diagnosis with kidney disease.

I have thought hard about why PD is not presented to patients as an initial option. In my case, it may not have made sense because of the perceived temporary nature of the condition. However, in a majority of other patients whose CKD is most definitely at stage 5 and he or she is going to need some form of RRT for the rest of his or life, PD is definitely an excellent option!

Then why this step-motherly treatment for this modality in India (and as I gather in many other parts of the world)?

One reason is patients themselves. I have talked to some patients about PD and find a reluctance to take care into their own hands. They are happy giving themselves up to the medical team and blame them for everything that is wrong with them. There is also the scare of infection. In India, very few patients on dialysis know about how rampant Hepatitis  C has become in dialysis units. With PD, yes, there is a risk of bacterial infection but the risk can be minimized if the patient is properly trained in aseptic techniques. With in-center hemodialysis, you are entirely at the mercy of the technicians and nurses. Hepatitis C is a very real danger due to their negligence.

Another reason could be nephrologists themselves. For some reason, nephrologists the world over have shied away from PD.

Another option that patients could be given is that of a transplant. Why wait even for a few months on dialysis? When the patient reaches Stage 5, start preparing for a transplant -  live related or cadaveric. Get everything in place and get a transplant as soon as necessary so that the patient does not need even a single session of dialysis.

These are all excellent options which the nephrologist must discuss with patients. All the options. Hemodialysis, Peritoneal Dialysis and a Transplant. The nephrologist (and possibly a trained counsellor) must explain all the three options well ahead of time and involve the patient and his or her family in the decision. Unlike today, when the nephrologist makes the decision for us.

It is my life. I want a say. Is this too much to ask?

By Kamal Shah

http://kamaldshah.com

http://dialysis.org.in

What Kamal is saying is not only true likely in India but in USA as well. This is an ongoing problem as more and more Younger Nephrologists don't feel well trained or comfortable in taking care of PD.  Meanwhile countries like Japan, have majority of their dialysis patients getting PD.  Economics or patient preferences- both might be a playing a role in this sad state of affairs.

Hypokalemia quiz answer

Labs on presentation: Na 117, K 1.5, Normal renal function. Exam consistent with volume depletion. EKG changes consistent with hypokalemia. Hyponatremia is asymptomatic

Treatment?

A. Treat hyponatremia first and then hypokalemia

B. Treat hyponatremia and hypokalemia simultaneously

C. Treat hypokalemia first and then hyponatremia  

Any thoughts? What would you do?
Here is what you all said:

" C,  but I believe that, in practice, we'd probably end up doing B."

"I would think treat both. As you improve distal tubular flow with saline , hypokalemia can worsen"

"How about KCl, NaCl and DDAVP with water restriction."

"Treat hypokalemia first.”

”In this case the hyponatremia may be at least partly explained by the huge deficit in total body potassium stores, thus causing intracellular shift of sodium in exchange for potassium. Given that this patient is asymptomatic, option C is probably the safest. Aggressive repletion of K w/150-200 mEq daily for 2-3 days will be necessary to replete his K and the patient's Na may slowly improve as well."


"Treat hypokalemia with IV KCL (ECG abnormalities make it urgent). Repleting volume would probably take care of hyponatremia."

"Patient should only be treated for Hypokalemia first as hypokalemia correction itself will cause improvement in hyponatremia. The theory behind it is with K repletion, there is translocation of K in the cell and Na will move out. Mich. Halperin book has an excellent article on this."

I think all responded practically the right answer. Correction of hypokalemia is very important in setting of hyponatremia and one has to be watchful of not over correcting Na too fast in this setting as correcting the K will correct the Na as one of the commenters pointed out. There have been cases reported of osmotic demyelination from just aggressive correction of K leading to fast Na correction.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/20338465

http://www.ncbi.nlm.nih.gov/pubmed/8192171

New York Academy of Medicine Nephrology Lecture:- Patient advocate

http://www.nyam.org/events/2011/2011-10-26.html

Check out this month- the new york academy of medicine will be presenting the ethical issues and the humanism behind CKD and dialysis care and how Nephrologists are the Best advocate for the patients with kidney disease.

ASN Podcast :Kidney Research National Dialogue Podcast

http://www.asn-online.org/publications/kidneynews/podcast.aspx

To visit the website for the KRND, go to http://krnd.ideascale.com/

Podocyte Disorders

Glomerular disease review in a nutshell- check out the latest offering from AJKD Core Topics review
http://www.ajkd.org/article/S0272-6386(11)01071-7/fulltext

Hemodialysis Patients and and their Risky Weekends, a conversation with the author of the recent NEJM paper

An odd asymmetry of hemodialysis is that almost all patients have treatments every other day, Wednesday and then Friday or Thursday and then Saturday; but then a 2 day break over the weekend. What happens from Friday to Monday or Saturday to Tuesday, is there increased risk? ( image source:  www.tws3d.com)

Robert Foley and colleagues from the United States Renal Data System studied exactly this question. Their study was published recently in the New England Journal of Medicine (N Engl J Med 2011;365:1099-107). A total of 32,065 hemodialysis patients from the Clinical Performance Measures Project were studied from 2004-2007. The main finding was that on the day after the long interdialytic period there was an approximately 20% increase in deaths, more than a 30% increase in deaths from cardiac causes, a 30% increase in deaths from cardiac arrest and a number of other outcomes with increased risk.

This simple but elegant study places a sharp focus on what may be intuitive, hemodialysis patients are at greater risk after the long interdialytic period- usually after a weekend. Is it excessive intake of salt, potassium and other electrolytes over the weekend? Increased volume intake? A reduction in calcium with widened QT intervals? Whatever the cause, we need to think about how hemodialysis may be changed to keep patients safer.

I asked Dr. Foley about what the clinical implications of these finding are. He responded, “Like all observational studies, cause and effect can't be proven here. However, unlike most observational studies, differences in unmeasured comorbidity can't explain the findings, as the same population is being examined for outcomes on different days. Given the downward-tilted sawtooth pattern for death and cardiovascular admissions, it is hard to imagine that anything other than more frequent dialysis and avoidance of two-day intervals could change the current situation. Clearly, this would involve major philosophical and logistical shifts.”

Post by

Steven Fishbane, MD

Prof of Medicine

Congress of Nephrology in Internet 2011

 The Organizing Comitee of 6th Congress of Nephrology in

Internet, CIN2011, is going to be held in November, probably right after the ASN meet 2011. 

It will be held next November 15-30th 

on http://cin2011.uninet.edu/

All presentations are online and from around the world. Its also free to attend. 

Should be a lot of fun.

Check it out

Gray's Anatomy Classic Collectors Edition : The Kidney

Gray's Anatomy is one of the classic well reputed anatomy text books of all time in history of medicine. Looking at a 1977 version under the urinary organs brings back some interesting terms used in older text books.

" The Kidneys, two in number,are situated in the back part of the abdomen, and are for the purpose of separating from the  blood certain materials which, when dissolved in a quantity of water , also separated from the blood by the kidneys, constitute the urine." - defines the function of the Kidneys.

"Minute Anatomy:- The tubuli uriniferi, of which the kidney is for the most part made up, commence in the cortical portion of the kidney, and, after pursuing a very circuitous course through the cortical and medullary parts of the kidney, finally terminate at the apices of the Malpighian pyramids by open mouths, so that the fluid which they contain is emptied into the dilated extremity of the ureter contained in the sinus of the kidney. "
- defines the role of the tubules

"Each of these little bodies is composed of two parts- a central glomerulus of vessels,called a Malphagian tuft and a membranous envelope, the Malphagian capsule, or Bowman's capsule, which latter is a small pouch-like commencement of a uriniferous tubule"- describes the glomerulus and connection to the tubule.

Ref:
Henry Grays'  Gray Anatomy 1977 edition.

IN THE News: A report about inducing tolerance in kidney transplants

A nice letter from investigators at Stanford published this week in NEJM Oct 2011 issue shows a proof of concept. 12 patients, got a HLA matched kidney and a donor cell infusion of CD34+ progenitor cells mixed with CD3+ T cells and irridiation and anti thymoglobuliun. The irridiation was not total body but more to spleen, thymus and lymph nodes. Giving stem cell transplantation and kidney transplant to a well matched patient led to chimerism and ultimately majority patients came off immunosuppresion and renal function is stable. Take a look at the full letter at

http://www.nejm.org/doi/full/10.1056/NEJMc1107841

"Hyponatremia" not that benign

I urge you all to read the piece from Annals of Internal Medicine by Sagalyn called
" A little hyponatremic". A beautifully written narrative of something we have to all keep in mind.

http://www.ncbi.nlm.nih.gov/pubmed/21969347

CONSULT ROUNDS: Hypokalemia and Osmotic Demyelination Syndrome

Labs on presentation: Na 117, K 1.5, Normal renal function. Exam consistent with volume depletion. EKG changes consistent with hypokalemia. Hyponatremia is asymptomatic

Treatment?

A. Treat hyponatremia first and then hypokalemia

B. Treat hyponatremia and hypokalemia simultaneously

C. Treat hypokalemia first and then hyponatremia  

Any thoughts? What would you do?

In the News:- TOLL like receptors and Nobel Prize in Medicine 2011

The nobel prize this year in 2011 for Medicine is going to the discovery of the Toll like receptors and dendritic cells. Check out the website of Nobel Prize at : http://www.nobelprize.org/nobel_prizes/medicine/laureates/2011/#
Some minor information.


Dendritic cell:- An antigen presenting cell is a very prominent cell now in our textbooks and especially when we deal with transplantation immunology. This was discovered by Ralph Steinman in 1973. He speculated that it could be important in the immune system and went on to test whether dendritic cells could activate T cells, a cell type that has a key role in adaptive immunity and develops an immunologic memory against many different substances. 
Toll like receptors: Bruce Beutler was searching for a receptor that could bind the bacterial product, lipopolysaccharide (LPS), which can cause septic shock, a life threatening condition that involves overstimulation of the immune system.  TLR were hence discovered. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes. They are more like pattern recognizing receptors. Three subgroups of TIR domains exist. Sub group 1 are receptors for interleukins, subgroup 2 directly to microbes, subgroup 3 to get signals from subgroup 1 and 2. 

image Source: Wikipedia.com

NSLIJ Transplant Surgeon on ABC

Dr Ernesto Molmenti, from our transplant department speaks about the gift of transplantation
Transplant Surgeon on

CLINICAL CASE 44: ANSWERS AND SUMMARY

34 YEAR OLD FEMALE, RECENT PREGNANCY,HAS SIGNIFICANT HYPERTENSIVE EPISODES AND IS ADMITTED. LABS SHOW MG OF 0.8. SHE HAS SLE ON STEROIDS AND TACROLIMUS. HX OF ITP NEEDING IVIG. WHAT(IN HER) ARE CAUSES OF POSTERIOR REVERSIBLE LEUKOENCEPHALOPATHY SYNDROME?

Pregnancy 22%

IVIG 25%
Tacrolimus 58%
Steroids 11%

SLE 38%

Hypomagnesemia 19%

Hmm... tough question but good try all.  In this particular patients, unfortunately she had all the risk factors and potentially known causes of Posterior Reversible Leukocencephalopathy Syndrome(PRES).

Known causes of PRES are: Pregnancy- pre eclampsia or eclampsia. SLE, Vasculitis, Uncontrolled hypertension from essential causes or secondary causes like medications ( steroids, tacrolimus), drug induced from chemotherapy like vincristine, anti VEGF agents, steroids, CNIs, IVIG are all risk factors.

TTP, HUS are known risk factors

Interestingly, hypomagnesemia, and hypocalcemia are noted to be risk factors as well.  

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/21572160

http://www.ncbi.nlm.nih.gov/pubmed/18495165

http://www.ncbi.nlm.nih.gov/pubmed/21856490